tbuckley/cabot-search huggingface dataset:
A novel nomogram could predict prognosis for multiple cancer patients with primary resistance to immune checkpoint inhibitors.
Authors: Xuanzong Li, Xinyu Fan, Linlin Wang
Journal: Journal of Clinical Oncology (2022)

e14561 Background: Cancer patients with immune checkpoint inhibitors (ICIs) treatment often experience unique progression response patterns, accounting for the discordance of short-term and long-term benefits. Identifying the specific characteristics of different quality progression disease (PD) events can maximize the curative effect of ICIs and further improve the prognosis of the patients with immunotherapy. In this study, we established a neutrophil-to-lymphocyte ratio (NLR)-based nomogram model which could predict survival for NSCLC patients with primary resistance to ICIs. Methods: Univariate and multivariate Cox regression analysis were used to evaluate the ability of each parameter to predict overall survival (OS). The regression coefficients obtained in multivariate analysis were visualized in the form of a nomogram, thus a new nomogram and risk classification system were established. The discrimination ability of the new model was evaluated using area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis. Survival curves were made by the Kaplan-Meier method and compared by the Log-rank test. Results: A total of 1235 patients with multiple cancer types who accepted at least one dose of ICIs treatment between 2015 and 2018 at Memorial Sloan Kettering Cancer Center were included in our study. Among them, 624 PD-patients (obtaining PD as their best response) were used to identify potential survival-related characteristics and build a nomogram model. Univariate and multivariate analysis demonstrated that pretreatment NLR, treatment lines and Eastern Cooperative Oncology Group performance status scores were independent prognostic factors and were included in the predictive model. The ROC curves implied the good discrimination ability of the predictive model with the AUC value for 1-year OS was 0.756. And, the calibration curves showed that the predicted value of the 1-year survival rate by the nomogram was in good agreement with the actual observed value of it. Based on the nomogram, we divided PD-patients into high-, med- and low-risk subgroups. The OS of cancer patients in three risk groups were accurately differentiated either in all PD-patients or PD-NSCLC-patients, but not in the patients who responded to ICIs. Importantly, the prognosis of the low-risk PD-patients was significantly better compared with the patients in med- and low-risk groups (P &lt; 0.001). Moreover, in the PD-patients with NSCLC, similar results were also found that patients had a worse OS in the high-risk group (P &lt; 0.001). Interestingly, in contrast to the results in PD-patients, a comparable OS between high-, med- and low-risk groups based on our model was verified in the patients who responded to ICIs. Conclusions: The pretreatment NLR-based nomogram could predict the prognosis for pan-cancer patients with primary resistance to ICIs treatment.
Evolutions in the management of non-small cell lung cancer in the 21st century: A bibliometric analysis from the 100 most impactful articles in the field.
Authors: Siyuan Chen, Yi Hu, Zhefeng Liu
Journal: Journal of Clinical Oncology (2022)

e20562 Background: The study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the 21 st century. Methods: The top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field. Results: The average citation of each retrieved top 100 most-cited NSCLC management papers in 21 st century was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n = 76), followed by Germany (n = 34), France (n = 33), and South Korea (n = 32). The top contributors were Paz-Ares L. (n = 12) and Reck M. (n = 12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n = 20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n = 33, citations =80427), followed closely by the Journal of Clinical Oncology (n = 28, citations = 32408). “Chemotherapy” (n = 36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (= 4.01), followed by “nivolumab” (= 3.85), “blockade” (= 2.86), and “efficacy” (= 2.85). Conclusions: The United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most papers on this topic in 21 st century. Individual authors, such as Paz-Ares L. and Reck M., have developed extensive international collaborations. The New England Journal of Medicine is the most eye-catching journal. Molecular, biological, and genetic research plays important role in this field. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Immunotherapy and combination therapy are research frontiers. To our knowledge, the study is the first bibliometric assessment on the evolution of NSCLC treatment from the 21 st century.
The interim result of a phase I/II study of nivolumab with or without ipilimumab in combination with multi-fraction stereotactic radiosurgery for recurrent, high-grade, radiation-relapsed meningioma.
Authors: Jiayi Huang, Feng Gao, Joshua Shimony, Tanner Michael Johanns, Megan Mantica, Timothy Robin Gershon, Douglas Edward Ney, Tolga Tuncer, Joe Sammy Mendez, Howard Streicher, Jian Li Campian
Journal: Journal of Clinical Oncology (2022)

2068 Background: There is a lack of effective therapy for recurrent high-grade meningiomas who relapsed after prior radiation therapy (RT). ETCTN 10186 is a phase I/II study to evaluate the feasibility and preliminary clinical efficacy of combining reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab for recurrent high-grade meningiomas. The preliminary results from the phase I portion are reported here. Methods: Recurrent grade II-III meningioma patients were treated with radiosurgery plus nivolumab with or without ipilimumab. Key eligibility criteria include age ≥ 18 years; ECOG score ≤ 2; tumor diameter 1-5 cm; prior radiation dose ≤ 70 Gy; normal organ function; no active autoimmunity. During the phase I portion, eligible patients were treated according to treatment-escalation schema following the modified 3+3 design (Table 1). The maximum tolerated combination (MTC) will be the regimen at which ≤ 1/6 patients experience dose-limiting toxicity (DLT) within 8 weeks of the start of study therapy. During the phase II portion, a total of 24 evaluable patients will be enrolled at the MTC using Simon’s MiniMax two-stage design. The primary endpoint of the phase I portion is to determine the MTC. Objective radiological responses (ORRs) are defined as per the Macdonald criteria. One cycle of immunotherapy is defined as 4 weeks of nivolumab with or without concurrent ipilimumab. Results: From 7/2019 to 3/2021, 13 patients were enrolled in the phase I, including 6 with regimen A and 7 with regimen B (Table). The median prior RT dose was 56 Gy (18-70) at a median interval of 2.8 years (1.3-13.3). There was no DLT in either cohort, so regimen B was deemed the MTC. The median cycles of immunotherapy completed were not significantly different between cohort A and B (11 vs. 6, p = 0.41, respectively). Three cohort A patients and 2 cohort B patients completed all planned doses of immunotherapy. Most patients stopped due to progression, and only one cohort B patient stopped due to treatment-related toxicity (grade 3 hypophysitis and encephalitis after 6 cycles of immunotherapy). After a median follow-up of 11.1 months, there have been 5 progressions and 4 deaths. The 6 month-PFS and 12 month-PFS rates are 62% and 54%, respectively. Two ORRs have been reported by institutional assessment, and central radiology review is ongoing and will be reported. Conclusions: Reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab are well tolerated for radiation-relapsed high-grade meningiomas. Phase II study of regimen B is currently enrolling. Clinical trial information: NCT03604978. [Table: see text]
Intratumor heterogeneity analysis in lung adenocarcinoma by single-cell RNA sequencing and construction of a prognostic gene signature.
Authors: Haifu Huang, Weiyu Wang, Tianhao Mu, Biqian Fu
Journal: Journal of Clinical Oncology (2022)

e20521 Background: Lung adenocarcinoma (LUAD), at the cellular level, has a high degree of intratumor heterogeneity. Advanced single-cell sequencing technologies have offered tools to analyze intratumor heterogeneity and identify the biomarkers, thereby aiding cancer diagnosis and prediction of the patient prognosis. Methods: From the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) database, the single-cell RNA sequencing (scRNA-seq) data from two LUAD and two para-cancerous tissue samples were obtained. We performed a dimensionality reduction and unsupervised clustering to identify the different cell clusters within the tumor tissues. To identify the most relevant modules and important cell subpopulations (clusters) in LUAD tissues, a weighted gene co-expression network analysis (WGCNA) was performed. Subsequently, we classified the LUAD molecular subtypes according to the marker genes of these clusters. The Limma package ( www.bioconductor.org/packages/release/bioc/html/limma ) was used to screen for the differentially expressed genes (DEGs) between the subtypes. Using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses, the gene signature most significantly associated with the prognosis of LUAD patients was determined. Results: A total of 14 cell clusters belonging to 10 cell types in LUAD was identified. The turquoise module was found to be the most relevant to LUAD among all the modules; cluster 10 (C10) was found to be the most strongly associated with the turquoise module. In The Cancer Genome Atlas (TCGA), patients with LUAD were divided into two groups of distinct molecular subtypes. Based on the 165 shared genes between the turquoise module and C10, 511 DEGs between the two molecular subtypes were obtained, and five of them were selected to construct the gene signature, which was validated to be an independent prognostic marker of LUAD. Conclusions: 14 cell clusters co-existed in LUAD, which contributed to its intratumor heterogeneity. In addition, two molecular subtypes of LUAD were identified and a five-gene signature was developed and validated to be significantly associated with prognostic and clinical characteristics of LUAD patients. Keywords: single-cell RNA sequencing, lung adenocarcinoma, intratumor heterogeneity, molecular subtypes, prognosis, five-gene signature.
Antitumor pharmacological activity of hybrid organotin compounds on the Lewis epidermoid carcinoma model.
Authors: Margarita Avdeevna Dodokhova, Inga Movlievna Kotieva, Andrey Vladimirovich Safronenko, Margarita Stefanovna Alkhuseyn-Kulyaginova, Elizaveta Мikhailovna Kotieva, Violetta Мikhailovna Kotieva, Sergey Igorevich Starostin, Evgeniy Aleksandrovich Nikitin, Dmitriy Borisovich Shpakovsky, Elena Rudolfovna Milaeva
Journal: Journal of Clinical Oncology (2022)

e15004 Background: New antitumor agents based on organic metal derivatives are intensively determined and created by now. Tin compounds are of great interest among them [Milaeva E.R.et al. Novel selective anticancer agents based on Sn and Au complexes. Pure &amp; Applied Chemistry. 2020, 92, 1201-1216]. The results of studies on cell line models allowed us to conclude that cytotoxic effect of organotin compounds is pronounced, so it is advisable to hold their further studies on biological models in vivo [ Dodokhova M.A. et al. Pharmacotherapeutic potential’s evaluation of organotin compounds in vivo Biopharmaceutical journal, 13(3), 30 – 34 (2021); doi: 10.30906/2073-8099-2021-13-3-30-34]. For the specialists of experimental pharmacology and oncology is relevant to rate the antitumor activity of hybrid organotin compounds on experimental malignant tumors. Methods: The study was held on C57Bl/6 mice (females, n = 36, each cohort contained 12 mice) on a Lewis epidermoid carcinoma model (subcutaneous transplantation) [Kit O.I. et al. Influence of chronic neurogenic pain on the dynamics of the no-system functioning during melanoma B16/F10 growth in male mice. Siberian Journal of Oncology, 2021, 20(3), 67–75]. Bis-(3,5-di-tert-butyl-4-hydroxyphenyl)dimethyl tin(Me-3) and (3,5–di–tert–butyl–4–hydroxyphenylthiolate) triphenyl tin (Me-5) were used as chemotherapeutic agents. Groups of animals were formed as follows: I (experimental) - Me-3 at a dose of 75 mg / kg; II (experimental) - Me-5 at a dose of 50 mg / kg; III (control group) - without pharmacological substances. The doses were characterized as the most effective according to the results of a pharmacological activity screening study. The compounds were injected intraperitoneally daily for 5 days. All animals were euthanized since 21 days after the tumor cells transplantation. The antitumor effect was estimated by the percentage of tumor growth inhibition by weight (%). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Results: After the intraperitoneal injection of chemical substances Me-3 and Me-5, there was revealed an inhibition of growth by weight of Lewis epidermoid carcinoma’s primary node for all experimental groups, 23.7% and 28% respectively. Conclusions: The injection of organotin compounds with different ligand groups allows us to suggest a biocidal activity of the organotin component on the primary tumor node cells.
Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systematic therapy of gastric cancer.
Authors: Miaozhen Qiu, Mingyu Lai, Wen-Long Guan, Yu-Ting Sun
Journal: Journal of Clinical Oncology (2022)

e16063 Background: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. However, the consistency of these two methods has not been determined. Therefore, we compared the prognostic value of TRG and RECIST 1.1 for gastric cancer (GC) patients and analyzed their consistency. Methods: Patients with gastric cancer who received preoperative chemotherapy or chemotherapy combined with immunotherapy and had record of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 is considered as consistent with CR or PR in RECIST 1.1 and TRG 2-3 corresponds to SD or PD in RECIST 1.1. The primary endpoints were disease free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Kaplan-Meier method and Cox proportional hazards regression models were used for survival analysis. Results: We enrolled 157 GC patients, including 125 patients with preoperative chemotherapy, and 32 patients with preoperative chemotherapy combined with PD-1 inhibitors. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results of RECIST 1.1 and TRG. The pCR rate was 13.4% and the overall response rate (ORR) was 52.6% according to RECIST 1.1. Preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone, 34.4% vs 8.0%, P&lt; 0.001. TRG was significantly correlated with both OS and DFS (P = 0.0162 and 0.0259, respectively) while response according to RECIST1.1 was not significantly related with OS and DFS ( P= 0.8598 and 0.2288, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. Young patient, peritoneal metastasis or liver metastasis was correlated with TRG 2-3. Conclusions: Our results showed that TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received neoadjuvant therapy.
Twice-daily thoracic radiotherapy for patients with locally advanced or oligometastatic non-small cell lung cancer: A single-center observational study.
Authors: Jiahua Lyu, Long Liang, Junchao Wang, Qifeng Wang, Lei Wu, Yi Wang, Gang Wan, Hongyuan Jia, Hansong Bai, Tao Li
Journal: Journal of Clinical Oncology (2022)

e21070 Background: Radiotherapy is standard treatment for locally advanced or oligometastatic non-small cell lung cancer (NSCLC). Once-daily thoracic radiotherapy of 60～66 Gy in 30～33 fractions is considered to be the most effective schedule in the past. The aim of this study was to investigate whether twice-daily thoracic radiotherapy improves survival and reduces toxicity. Methods: Patients aged 18 years and older with treatment-naive confirmed locally advanced or oligometastatic NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. Participants received thoracic radiotherapy of 40～80 Gy(2～4Gy/fraction, bid) and 30～60 Gy (1.5～2.0Gy/fraction, bid) to the primary lung tumour and positive lymph node metastases respectively. Patients received 2-4 cycles of chemotherapy or oral targeted drugs if the driver genes is positive. Results: In total, 124 patients were included in this study between February 2016 to March 2020. The median patient age was 61 years old and 113(91.1%) patients were male. The patient group included 72 patients with stage IIB～IIIC, and 52 patients with stage IV disease. Histological diagnosis was squamous cell carcinoma in 68 patients, adenocarcinoma in 56 patients. Median follow-up was 24.8 months (range 1.5-59.7months). The 1, 2, 3-year OS were 83.1% and 70.6%, 60.6%, respectively. The incidence of ≥Grade 2 radiation pneumonitis and esophagitis were was 25.6% and 15.2%, respectively. The most common grade 3-4 adverse events were leukopenia (17 [13.7%]), thrombocytopenia (5 [4.0%]), anaemia (15[12.0%]) and lymphopenia (30[24.2%]). None of the patients experienced fatal bronchopulmonary hemorrhage or tracheal fistula. Conclusions: Twice-daily thoracic radiotherapy is feasible and well tolerated for locally advanced or oligometastatic NSCLC. It needs to be further confirmed by large randomized controlled clinical studies. Clinical trial information: ChiCTR2100055096.
Development and validation of longitudinal c-reactive protein as dynamic response predictor for PD-L1 blockade in advanced NSCLC: Findings from four atezolizumab clinical trials.
Authors: Jian-Guo Zhou, Xiaofei Chen, Ada Hang-Heng Wong, Haitao Wang, Fangya Tan, Si-Si He, Gang Shen, YunJia Wang, Ruihong Wang, Shamus R. Carr, Benjamin Frey, Rainer Fietkau, Markus Hecht, Hu Ma, David S. Schrump, Udo S Gaipl
Journal: Journal of Clinical Oncology (2022)

e21113 Background: Numerous studies suggested that pre-treatment C-reactive protein (CRP) is a survival predictive biomarker for cancer patients treated with anti-PD-(L)1 blockade. However, the application of longitudinal CRP levels as dynamic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with anti-PD-(L)1 remains unexplored. Methods: This study analyzed four international, multi-center clinical trials (OAK, BIRCH, POPLAR and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment. CRP test was performed ≤ 96 hours before Day 1 of each cycle. 1438 patients with more than 2 times CRP results (a total of 11,253 records) in all 3 collection timepoints. The primary endpoint was overall survival (OS). First, multivariate survival analysis was conducted to include clinical factors such as gender, ECOG-PS, race and metastases as contributing risk factors. Then, multivariate joint modelling of longitudinal and time-to-event data was used to establish the relationship between longitudinal CRP and OS in the OAK study, whereas external validation was performed by time-dependent AUC analysis on the BIRCH, POPLAR and FIR studies. Results: Log-transformed longitudinal CRP levels (log(CRP)) in combination with clinical factors in absence of PD-L1 expression emerged as independent predictors of worse OS in the OAK study (HR of jointed model = 2.08, 95% CI: 1.84-2.35, p &lt; 0.001) with a high accuracy (AUC = 0.74) for predicting OS. The predictive value of longitudinal CRP was validated in the external validation cohorts with good performance in OS (BIRCH: HR = 2.77 (95% CI: 2.31-3.44), AUC = 0.76; POPLAR: HR = 1.95 (95% CI: 1.50-2.64), AUC = 0.76; and FIR: HR = 1.83 (95% CI: 1.46 -2.39), AUC = 0.72). Conclusions: The Bayesian multivariate joint model demonstrated that longitudinal CRP is a strong survival dynamic predictor for atezolizumab-treated NSCLC patients.
Surgical intervention of hepatocellular carcinoma with wedge versus segmental resection: A SEER database analysis.
Authors: Ashton Legenza, Connor Tupper, Michael Burdyny, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e16136 Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, constituting 75-85% of liver cancer cases globally. In recent years there have been developments in both the clinical treatment methods and surgical approaches to HCC treatment, however, the prognosis for patients with HCC remains dismal. Two of the major surgical treatment options for HCC are wedge resections and segmental resection with the latter having up to three segments of the liver being removed. This study assessed the prognostic impact between these two surgical treatment options in the management of HCC liver cancer. Methods: We searched the SEER-18 database for HCC cases (histology codes 8170-8175) diagnosed between 2000-2018. Patients were excluded if their cause of death was not associated with their HCC diagnosis according to SEER’s cancer-specific death categorization. The SEER database tracks survival up to 60 months. Using SPSS, we performed analyses on the association between surgical subtype and survival, which is tracked up to 60 months in the SEER database. Results: A total of 3919 patients were collected from this search. Of that patient collection, 643 patients received a wedge resection and a total of 2609 patients received a segmental resection. There were 366 patients that received a segmental resection with local tumor destruction. 667 patient resections were not differentiated between segmental or wedge resections. The segmental resection of an unspecified number, the one segment resection, and the two segments resection groups all had better mean survival compared to the wedge resection group and segmental resection with local tumor destruction group (all p &lt; 0.05). The three segments resection compared to wedge resection had no difference in survivability (p &gt; 0.05). The three-segment resection had worse survivability when compared to both one and two-segment resections (p &lt; 0.01). The one-segment resection had no difference in survivability when compared to the two-segment resection procedure (p &gt; 0.05). Conclusions: Though limitations of small sample size and univariate statistical analyses were present in this study, one or two segment resection is associated with improved survival compared to wedge resection, the three segment resection and the segmental with local tumor destruction approach used in the treatment of HCC.[Table: see text]